Population Genetics of Plasmodium vivax in the Peruvian Amazon

Abstract

BackgroundCharacterizing the parasite dynamics and population structure provides useful information to understand the dynamic of transmission and to better target control interventions. Despite considerable efforts for its control, vivax malaria remains a major health problem in Peru. In this study, we have explored the population genetics of Plasmodium vivax isolates from Iquitos, the main city in the Peruvian Amazon, and 25 neighbouring peri-urban as well as rural villages along the Iquitos-Nauta Road.Methodology/ ResultsFrom April to December 2008, 292 P. vivax isolates were collected and successfully genotyped using 14 neutral microsatellites. Analysis of the molecular data revealed a similar proportion of monoclonal and polyclonal infections in urban areas, while in rural areas monoclonal infections were predominant (p = 0.002). Multiplicity of infection was higher in urban (MOI = 1.5–2) compared to rural areas (MOI = 1) (p = 0.003). The level of genetic diversity was similar in all areas (He = 0.66–0.76, p = 0.32) though genetic differentiation between areas was substantial (PHIPT = 0.17, p<0.0001). Principal coordinate analysis showed a marked differentiation between parasites from urban and rural areas. Linkage disequilibrium was detected in all the areas ( = 0.08–0.49, for all p<0.0001). Gene flow among the areas was stablished through Bayesian analysis of migration models. Recent bottleneck events were detected in 4 areas and a recent parasite expansion in one of the isolated areas. In total, 87 unique haplotypes grouped in 2 or 3 genetic clusters described a sub-structured parasite population.Conclusion/SignificanceOur study shows a sub-structured parasite population with clonal propagation, with most of its components recently affected by bottleneck events. Iquitos city is the main source of parasite spreading for all the peripheral study areas. The routes of transmission and gene flow and the reduction of the parasite population described are important from the public health perspective as well for the formulation of future control policies.

Epidemiology of Plasmodium vivax Malaria in Peru

“…A recent longitudinal study conducted over 25 different villages (among five study areas) confirmed these findings, showing that study areas along the highway from Iquitos to Nauta (cluster A2 and A3) had higher MOI (1.5–2) than isolated communities with low mobility (cluster A1, A4, and A5). However, H e was high in all communities ( H e 0.66–0.76) 76. On the other hand, in San Carlos, a relatively small and isolated village, at 10 km from the Iquitos–Nauta road, genetic diversity and MOI were constrained ( H e = 0.49, MOI = 1.1) 71,74.…”

Gene flow and genetic drift in urban environments

“…To test whether the urban landscape is indeed the main factor driving these differences in genetic drift and gene flow between urban and nonurban populations, many studies have used a landscape genetics approach (Beninde, Feldmeier, Veith, & Hochkirch, ; Delgado‐Ratto et al, ; Thomassen et al, ; Wood et al, ; Yakub & Tiffin, ). This approach allows researchers to identify potential barriers or conduits to gene flow between populations and make inferences about the effects of the landscape on evolutionary processes.…”

Monitoring of Plasmodium falciparum and Plasmodium vivax using microsatellite markers indicates limited changes in population structure after substantial transmission decline in Papua New Guinea

“…P. vivax population genetic analyses in the South West Pacific region, reveal a modest decline in diversity and increasing population structure with the eastward decline in transmission (Fola et al, 2017;Koepfli et al, 2013;Waltmann et al, 2018). However, a clear signature of significant mLD has been observed at low transmission in several studies suggesting increasingly focal transmission as malaria rates decline, and the increasing contribution of genetically similar relapses as new infections become rarer Batista et al, 2015;Chenet et al, 2012;Delgado-Ratto et al, 2016;Ferreira et al, 2007;Imwong et al, 2007;Iwagami et al, 2012;Noviyanti et al, 2015;Orjuela-Sanchez et al, 2013). P. vivax has higher diversity compared to P. falciparum which is consistent with a longer association with humans (Gilabert et al, 2018;Hupalo et al, 2016;W.…”

“…Regional surveys reveal source and sink populations and parasite migration in a country and can help to predict whether and where targeted interventions would be effective and the spatial scale required (Auburn & Barry, 2017;Koepfli & Mueller, 2017). Fine-scale population genetic surveys also identify local drivers contributing to sustained transmission such as particular human social and economic interactions Delgado-Ratto et al, 2016;Koepfli & Mueller, 2017). While parasite population genetics and genomics is becoming more popular and accessible, the impact on control programs has been limited, and to date few studies have systematically assessed the long-term impact of malaria control using these approaches (Batista, Barbosa, Da Silva Bastos, Viana, & Ferreira, 2015;Bei et al, 2018;Branch et al, 2011;Chenet, Taylor, Blair, Zuluaga, & Escalante, 2015; R. F. Daniels et al, 2015;Gatei et al, 2010;Gunawardena, Ferreira, Kapilananda, Wirth, & Karunaweera, 2014;Iwagami et al, 2012;Salgueiro, Vicente, Figueiredo, & Pinto, 2016;Vardo-Zalik et al, 2013).…”

“…For P. vivax, a less virulent but nevertheless significant human pathogen, the picture is different. The impact of relapse and other unique features of P. vivax biology (Olliaro et al, 2016) on underlying transmission dynamics is evidenced by higher genetic diversity and multiclonal infections, even at low transmission (Arnott et al, 2013;Barry et al, 2015;Batista et al, 2015;Chenet et al, 2012;Delgado-Ratto et al, 2016;Ferreira et al, 2007;Fola et al, 2017;Fola et al, 2018;Gunawardena et al, 2014;Hong et al, 2016;Iwagami et al, 2012;Jennison et al, 2015;Koepfli, Rodrigues, et al, 2015;Noviyanti et al, 2015;Orjuela-Sanchez et al, 2013;Pava et al, 2017;Waltmann et al, 2018). P. vivax population genetic analyses in the South West Pacific region, reveal a modest decline in diversity and increasing population structure with the eastward decline in transmission (Fola et al, 2017;Koepfli et al, 2013;Waltmann et al, 2018).…”